TY - JOUR
T1 - Conformational and membrane interaction studies of the antimicrobial peptide alyteserin-1c and its analogue [E4K]alyteserin-1c
AU - Subasinghage, Anusha P.
AU - O'Flynn, Donal
AU - Conlon, J. Michael
AU - Hewage, Chandralal M.
N1 - Funding Information:
We are grateful to University College Dublin for Research Demonstrator ship to AS and DOF. Authors would like to acknowledge the funding from Science Foundation Ireland to AS and for the NMR spectrometer upgrade, and to the United Arab Emirates University for a Faculty Support Grant ( NP-10-11/103 ) to JMC. Authors would like to thank Prof. Lena Maler, Department of Biochemistry and Biophysics, Stockholm University, Sweden for valuable input regarding the membrane interaction studies with paramagnetic agents. Structural coordinates and chemical shifts for alyteserin-1c were deposited in the PDB (2L5R) at BMRB (17281).
PY - 2011/8
Y1 - 2011/8
N2 - Alyteserin-1c (GLKEIFKAGLGSLVKGIAAHVAS.NH2), first isolated from skin secretions of the midwife toad Alytes obstetricans, shows selective growth-inhibitory activity against Gram-negative bacteria. The structures of alyteserin-1c and its more potent and less haemolytic analogue [E4K]alyteserin-1c were investigated in various solution and membrane mimicking environments by proton NMR spectroscopy and molecular modelling. In aqueous solution, the peptide displays a lack of secondary structure but, in a 2,2,2-trifluoroethanol (TFE-d3)-H2O solvent mixture, the structure is characterised by an extended alpha helix between residues Leu 2 and Val21. Solution structural studies in the membrane mimicking environments, sodium dodecyl sulphate (SDS), dodecylphosphocholine (DPC), and 1,2-dihexanoyl-sn-glycero-3-phosphatidylcholine (DHPC) micelles, indicate that these peptides display an alpha helical structure between residues Lys3 and Val21. Positional studies of the peptides in SDS, DPC and DHPC media show that the N-terminal and central residues lie inside the micelle while C-terminal residues beyond Ala19 do not interact with the micelles.
AB - Alyteserin-1c (GLKEIFKAGLGSLVKGIAAHVAS.NH2), first isolated from skin secretions of the midwife toad Alytes obstetricans, shows selective growth-inhibitory activity against Gram-negative bacteria. The structures of alyteserin-1c and its more potent and less haemolytic analogue [E4K]alyteserin-1c were investigated in various solution and membrane mimicking environments by proton NMR spectroscopy and molecular modelling. In aqueous solution, the peptide displays a lack of secondary structure but, in a 2,2,2-trifluoroethanol (TFE-d3)-H2O solvent mixture, the structure is characterised by an extended alpha helix between residues Leu 2 and Val21. Solution structural studies in the membrane mimicking environments, sodium dodecyl sulphate (SDS), dodecylphosphocholine (DPC), and 1,2-dihexanoyl-sn-glycero-3-phosphatidylcholine (DHPC) micelles, indicate that these peptides display an alpha helical structure between residues Lys3 and Val21. Positional studies of the peptides in SDS, DPC and DHPC media show that the N-terminal and central residues lie inside the micelle while C-terminal residues beyond Ala19 do not interact with the micelles.
KW - AMP
KW - Alyteserin
KW - Antimicrobial
KW - Molecular modelling
KW - NMR
KW - Positional studies
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U2 - 10.1016/j.bbamem.2011.04.012
DO - 10.1016/j.bbamem.2011.04.012
M3 - Article
C2 - 21565166
AN - SCOPUS:79958087317
SN - 0005-2736
VL - 1808
SP - 1975
EP - 1984
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 8
ER -